Project Summary/Abstract Meditation training is a promising technique that can help improve emotional health of adolescents and facilitate treatment of adolescent depression. However, there is a fundamental gap in understanding the neural reorganization that takes place as a result of meditation training. Continued existence of this gap represents an important problem because, until it is filled, design of more effective interventions is highly unlikely. The long- term goal is to establish safe and effective methods of promoting emotional health in adolescents. The objective here is to study adolescents undergoing meditation training by using MRI connectomics to map changes in node strength (integrated connectivity) of the putamen. The putamen is a region previously associated with meditation practice and attenuated shrinkage with age in Zen meditators on the one hand, and with love, compassion, anticipation of pleasure, and responses to increasing intensity of happiness on the other hand. The central hypothesis is that structural connectivity of the putamen with other brain regions will increase in adolescents with mediation training and, in turn, positively affect their emotional health. This innovative model is rooted in preliminary results and previous literature. The rationale for the proposed MRI connectomics approach is that regular engagement of the putamen is expected to increase myelination of the white matter tracks connecting it to other regions, which can be probed by using diffusion MRI. Guided by strong preliminary data, this hypothesis will be tested by pursuing two specific aims, which entail studying changes in the putamen node strength and emotional health measured as internalizing problems and depressive symptoms in 1) a cohort of healthy adolescents with a 12-week meditation training compared to waitlist controls (R61 phase) and 2) a cohort of adolescents with mild to moderate depression with a 12-week meditation training compared to waitlist controls (R33 phase). The ?Go/No-Go Criterion? is a medium-large increase of the putamen node strength observed with meditation training in healthy adolescents in the R61 phase (Cohen's d>0.6). The optimization strategy for the R33 phase is based on the fact that anhedonia (diminished ability to experience pleasure) is a key characteristic of depression and preliminary results show that putamen structural connectivity is lower in adolescent depression. It is therefore expected that the mechanistic effect in the putamen will be amplified in the population of depressed adolescents, reflecting normalization of the putamen function. The proposed research is innovative, because it uses advanced MRI connectomics methods to map changes in brain networks of youth with meditation training and tests a novel mechanistic model. The proposed research is significant, because it is expected to greatly advance our understanding of the neural mechanism by which meditation improves emotional health of adolescents. Ultimately, such knowledge will inform treatment and prevention of adolescent depression.